Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, Kaohsiung.
Department of Pharmacy, E-Da Hospital, I-Shou University, Kaohsiung.
Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620937194. doi: 10.1177/1753466620937194.
Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations.
We searched several databases and manufacturers' websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations.
We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79-1.18; = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90-1.03; = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81-1.03; = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86-1.00; = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52-64 weeks).
This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD.
长效毒蕈碱拮抗剂（LAMA）单药治疗被推荐用于有高加重风险的慢性阻塞性肺疾病（COPD）患者。长效β2-激动剂（LABA）/LAMA 固定剂量组合（FDC）在预防加重方面是否优于单独的 LAMA 尚不清楚。本研究旨在系统回顾文献，以调查 LABA/LAMA FDC 是否比 LAMA 单药治疗更能预防加重。
我们搜索了多个数据库和制造商的网站，以确定比较 LABA/LAMA FDC 治疗与单独使用 LAMA 治疗 ⩾24 周的相关随机临床试验。我们关注的结局是首次加重的时间和中重度、重度和所有加重的发生率。
我们纳入了 2013 年至 2018 年的 9 篇文章中的 10 项试验，共有 19369 名患者纳入本研究进行分析。与 LAMA 单药治疗相比，LABA/LAMA FDC 在首次加重时间方面显示出相似的疗效[风险比，0.96；95%置信区间（CI）0.79-1.18； = 0.71]、中重度加重[风险比（RR），0.96；95%CI 0.90-1.03； = 0.28]、重度加重（RR，0.92；95%CI 0.81-1.03； = 0.15），在所有加重方面有轻微优势[RR，0.92；95%CI 0.86-1.00； = 0.04]。在有既往加重史和治疗时间较长（52-64 周）的 COPD 患者中，LABA/LAMA FDC 组的所有加重事件发生率较低。
本研究提供了证据，表明与 LAMA 单药治疗相比，LABA/LAMA FDC 对 COPD 患者的所有加重预防有轻微优势。
